Deep polarization of the ensemble nitrogen-vacancy centers in diamonds induced by an Airy beam with a long focal depth.

Solid-state spin systems with nitrogen-vacancy (NV) centers in diamonds constitute an increasingly popular platform for quantum sensing. However, most existing platforms designed with ensemble NV centers exhibit a sensitivity that is significantly less than the theoretical maximum. This low sensitivity limits the expansion of the experimental results and application areas. In this study, the sensitivity is improved by increasing the pumping depth of the excitation beam to increase the number of particles involved in spin polarization at a given laser intensity. Compared with the proposed Airy beam with a long focal depth (25.46 λ) and the widely utilized Gauss beam pumping ensemble NV centers, the spin resonance factor fSR can be improved by 10.02%. This sensitivity-optimized approach enhances the functionality of sensors with NV centers.

Self-healing propagation of a longitudinally varying vector optical beam for distance measurement.

Based on the longitudinal manipulation of polarization, a special vector optical beam (VOB) with customized polarization variation in propagation direction can be generated, whose properties and applications remain to be studied. Here, the self-healing propagation behaviors of the longitudinally varying VOB after an opaque object are investigated, and the localized polarization responses on the object distance are revealed. On this basis, characteristic parameters are defined to measure the distance of object, achieving a minimum relative error of 0.63% in a longitudinal range of 300 mm. Besides, the correlations and uncoupling methods of object distance and size are discussed. Our studies open new ways to use the structural properties of VOB and may be instructive for laser measurement.

Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.

Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.

Analysis of the differential expression of serum miR-21-5p, miR-135-5p, and miR-155-5p by Bifidobacterium triplex viable capsules during the perioperative stage of colorectal cancer.

OBJECTIVE: In this study, we investigated the impact of perioperative administration of Bifidobacterium triplex viable capsules on the serum levels of circulating miR-21-5p, miR-135-5p, and miR-155-5p in patients with colorectal cancer (CRC). The purpose of this study is to provide a foundation for future research on the use of Bifidobacterium triplex viable capsules to enhance postoperative recovery in patients with CRC. METHODS: A total of 60 patients with primary CRC admitted to the Department of General Surgery at Shanxi Bethune Hospital between June 2020 and December 2020 were selected and randomly divided into two groups: 20 cases in the control group and 40 cases in the experimental group. The experimental group was administered oral Bifidobacterium triplex viable capsules during the perioperative period, while the control group was administered oral placebo. Before and after the perioperative period, the expression levels of miR-21-5p, miR-135-5p, and miR-155-5p were compared in the serum of both groups of patients. Furthermore, we established the prognostic value of these three miRNAs in CRC patients. RESULTS: After surgery, the expression levels of miR-21-5p, miR-135-5p, and miR-155-5p decreased in both groups of patients (P < 0.05). Significantly greater differences were observed between miR-21-5p and miR-135-5p (P < 0.001). Expression levels of serum miR-21-5p (P = 0.020) and miR-135-5p (P = 0.023) decreased significantly more in the experimental group than in the control group. The levels of the above three miRNAs after surgery did not correlate with 3-year OS (HR = 4.21; 95% CI 0.37-47.48; log-rank P = 0.20) or 3-year DFS (HR = 1.57; 95% CI 0.32-7.66; log-rank P = 0.55) in two groups. CONCLUSION: Radical surgery reduces the levels of serum miR-21-5p, miR-135-5p, and miR-155-5p expression in patients with CRC. The use of Bifidobacterium triplex viable capsules assists in achieving quicker perioperative recovery from radical surgery in CRC patients, and this underlying mechanism may be associated with the regulation of serum miR-21-5p, miR-135-5p, and miR-155-5p expression levels.

Role of thrombospondin-1 in high-salt-induced mesenteric artery endothelial impairment in rats.

The matrix glycoprotein thrombospondin-1 (THBS1) modulates nitric oxide (NO) signaling in endothelial cells. A high-salt diet induces deficiencies of NO production and bioavailability, thereby leading to endothelial dysfunction. In this study we investigated the changes of THBS1 expression and its pathological role in the dysfunction of mesenteric artery endothelial cells (MAECs) induced by a high-salt diet. Wild-type rats, and wild-type and Thbs1-/- mice were fed chow containing 8% w/w NaCl for 4 weeks. We showed that a high salt diet significantly increased THBS1 expression and secretion in plasma and MAECs, and damaged endothelium-dependent vasodilation of mesenteric resistance arteries in wild-type animals, but not in Thbs1-/- mice. In rat MAECs, we demonstrated that a high salt environment (10-40 mM) dose-dependently increased THBS1 expression accompanied by suppressed endothelial nitric oxide synthase (eNOS) and phospho-eNOS S1177 production as well as NO release. Blockade of transforming growth factor-ß1 (TGF-ß1) activity by a TGF-ß1 inhibitor SB 431542 reversed THBS1 up-regulation, rescued the eNOS decrease, enhanced phospho-eNOS S1177 expression, and inhibited Smad4 translocation to the nucleus. By conducting dual-luciferase reporter experiments in HEK293T cells, we demonstrated that Smad4, a transcription promoter, upregulated Thbs1 transcription. We conclude that THBS1 contributes to endothelial dysfunction in a high-salt environment and may be a potential target for treatment of high-salt-induced endothelium dysfunction.

Arbitrary combinations of helical-conical optical beams in free space.

Helical-conical optical beams (HCOBs) have attracted considerable interest due to their peculiar optical features. Their characteristic helical light intensity distribution has exerted unprecedented advantages in many fields, but multiple combinations of HCOBs have not been reported due to the limitations of algorithms and light field modulation techniques. We propose and experimentally demonstrate arbitrary combinations of multiple HCOBs in free space to construct hybrid HCOB arrays. The similarity between the experimental results and the numerical simulation results is 94.22%. The initial orientation of the HCOBs is flexibly tuned by the rotation factor ß, and the optical pen is used to combine the HCOBs. This approach allows multiple parameters in the array to be precisely tuned, including the type, number, and position of HCOBs, adding more design flexibility. The constructed HCOB arrays have a higher degree of modulation freedom and may find applications in fields where dynamic control is in high demand, including optical tweezers, biological cell sorting, and multiparticle manipulation.

Tight focusing of the vector optical field with polarization varying along complex curves of the Poincaré sphere.

Different from the scalar optical field with spatially uniform polarization, the vector optical field exhibits inhomogeneous distribution of polarization on the cross section. Manipulating the variation of polarization in a single optical beam is important to acquire a flexible and controllable focused optical field. Previous studies mainly focused on the vector optical field with its polarization varying along a circular trajectory of the Poincaré sphere. Here, we demonstrate the tight focusing behaviors of the vector optical field with the polarization varying along complex curves of the Poincaré sphere, which is generated by the joint modulation of azimuthal phase and amplitude distributions of orthogonally polarized components. The longitudinal polarization component with a multipolar pattern in rotational symmetry can be achieved with similar distribution of the total focused field. The transverse and longitudinal spin angular momentum distributions in the focal space are discussed. Approximately pure transverse spin angular momentum can be constructed and manipulated in the focal space, which provides the possibility to manipulate the 3D spin flux for the applications of nano and spin photonics.

Single centre analysis of factors influencing surgical treatment of splenic trauma in children.

OBJECTIVE: This study aims to investigate determinants impacting the surgical management of splenic trauma in paediatric patients by scrutinizing age distribution, etiological factors and concomitant injuries. The analysis seeks to establish a foundation for delineating optimal operative timing. METHODS: A cohort of 262 paediatric cases presenting with splenic trauma at our institution from January 2011 to December 2021 underwent categorization into either the conservative or operative group. RESULTS: Significantly disparate attributes between the two groups included age, time of presentation, blood pressure, haemoglobin levels, blood transfusion requirements, thermal absorption, American Association for the Surgery of Trauma (AAST) classification and associated injuries. Logistic regression analysis revealed age, haemoglobin levels, AAST classification and blood transfusion as autonomous influencers of surgical intervention (OR = 1.024, 95% CI: 1.011-1.037; OR = 1.067, 95% CI: 1.01-1.127; OR = 0.2760, 95% CI: 0.087-0.875; OR = 7.873, 95% CI: 2.442-25.382; OR = 0.016, 95% CI: 0.002-0.153). The AAST type and age demonstrated areas under the receiver operating characteristic (ROC) curve of 0.782 and 0.618, respectively. CONCLUSION: Age, haemoglobin levels, AAST classification and blood transfusion independently influence the decision for surgical intervention in paediatric patients with splenic trauma. Age and AAST classification emerge as viable parameters for assessing and prognosticating the likelihood of surgical intervention in this patient cohort.

[Establishment and content validity assessment of evaluation index system for development value of traditional Chinese medicine preparations in medical institutions].

The development of traditional Chinese medicine(TCM) preparations as an incubator for new drugs in medical institutions has flourished, while an evaluation index system remains to be established for comprehensively assessing the development value of these prescriptions. This study established an item pool through literature research, employed the Delphi method to determine the content of evaluation indexes, and adopted the superiority chart to determine the weight of each index. Two-level evaluation index system for the development value of TCM preparations in medical institutions was established, which included 7 first-level items and 36 se-cond-level items, demonstrating scientific validity. The first-level items(weight) were inheritance(10.61%), effectiveness(23.22%), safety(22.71%), innovation(13.21%), economy(10.00%), suitability(8.57%), and accessibility(11.68%). The top three second-level items in terms of weight distribution were adverse reaction monitoring(6.73%), evidence of therapeutic effect(5.71%), and clinical response rate(4.75%). The bottom three second-level items were production advantages(0.86%), medicinal dosage(0.48%), and medicinal smell or taste(0.18%). The content validity of the established system was assessed, which revealed that the index system was reliable, with the overall and average content validity indexes of 0.47 and 0.90, respectively. Furthermore, the established evaluation index system was used to evaluate six TCM preparations in a city-level hospital of TCM in Sichuan Province, which demonstrated that the system had operability. The results indicate that the evaluation index system is scientific, reliable, and operable, providing a reference for developers to selectively develop TCM preparations in medical institutions. In practical application, the system can be adjusted regarding the index weights according to actual conditions.

Polyoxometalate-Organic Hybrid "Calixarenes" as Supramolecular Hosts.

Calixarenes are among the most useful and versatile macrocycles in supramolecular chemistry. The one thing that has not changed in the 80 years since their discovery, despite numerous derivatizations, is their fully organic, covalent scaffolds. Here, we report a new type of organic-inorganic hybrid "calixarenes" constructed by means of coordination-driven assembly. Replacing acetate ligands on the {SiW10 Cr2 (OAc)2 } clusters with 5-hydroxyisophthalates allows these 95° inorganic building blocks to be linked into bowl-shaped, hybrid "calix[n]arenes" (n=3, 4). With a large concave cavity, the metal-organic calix[4]arene can accommodate nanometer-sized polyoxoanions in an entropically driven process. The development of hybrid variants of calixarenes is expected to expand the scope of their physicochemical properties, guest/substrate binding, and applications on multiple fronts.

Orientation of the NV centers are determined using the cylindrical vector beam array.

The determination of nitrogen-vacancy centers plays an important role in quantum information sensing. Efficiently and rapidly determining the orientation of multiple nitrogen-vacancy center s in a low-concentration diamond is challenging due to its size. Here, we solve this scientific problem by using an azimuthally polarized beam array as the incident beam. In this paper, the optical pen is used to modulate the position of beam array to excite distinctive fluorescence characterizing multiple and different orientations of nitrogen-vacancy centers. The important result is that in a low concentration diamond layer, the orientation of multiple NV centers can be judged except when they are too close within the diffraction limit. Hence, this efficient and rapid method has a good application prospect in quantum information sensing.

CD147 promotes breast cancer migration and invasion by inducing epithelial-mesenchymal transition via the MAPK/ERK signaling pathway.

BACKGROUND: CD147, a transmembrane glycoprotein, has been implicated in various cancer-related processes but its role in breast cancer remains poorly understood. Herein, we investigated the expression of CD147 in different breast cancer cell lines and explored its functional roles, including migration, invasion, drug resistance and modulation of key proteins associated with cancer progression. METHODS: The expression of CD147 was assessed in MCF-10 A, BT549, MDA-MB-231 and MCF-7 breast cancer cell lines using qRT-PCR and Western blotting, following which lyposome transfections were performed, leading overexpression of CD147 in BT549 cells and knockdown of CD147 in MCF-7 cells. Scratch assays and Transwell invasion and were performed to evaluate the cells' migration and invasion abilities. Sensitivity to 5-FU was determined via CCK-8 assays, and the expression of Snail1, E-cadherin, Vimentin, MMP-9 and the MAPK/ERK pathway were analyzed by qRT-PCR and Western blotting. RESULTS: Compared with normal beast epithelial cells, CD147 was highly expressed in all breast cancer cell lines, with the highest overexpression observed in MCF-7 cells and the lowest overexpression observed in BT549 cells. Overexpression of CD147 in BT549 cells increased, migration, invasion, viability and resistance to 5-FU of BT549 cells, while CD147 knockdown in MCF-7 cells reduced these properties of MCF-7 cells. Furthermore, CD147 influenced the expression of Snail1, Vimentin, E-cadherin, and MMP-9, suggesting its involvement in epithelial-mesenchymal transition (EMT) regulation. The MAPK/ERK pathway was activated by CD147 in BT549 cells, as indicated by increased p-MEK/MEK ratio and p-ERK/ERK ratio. In contrast, CD147 silencing in MCF-7 cells resulted in reduced p-MEK/MEK ratio and p-ERK/ERK ratio. CONCLUSION: In summary, our findings suggest CD147 as a potential therapeutic target in breast cancer treatment, particularly in cases where drug resistance and metastasis are concerns, worthy of further explorations.

Associations between gut microbiota and Parkinson disease: A bidirectional Mendelian randomization analysis.

BACKGROUND AND PURPOSE: Parkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in humans. METHODS: We performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases). RESULTS: Twelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval [CI] = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition. CONCLUSIONS: These results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.

[Efficacy analysis of autologous facet joint bone block in lumbar interbody fusion of osteoporosis patients].

OBJECTIVE: To compare and analyze the feasibility of autologous facet joint bone block as an alternative to polyetheretherketone (PEEK) cage in lumbar intervertebral fusion surgery for patients with osteoporosis. METHODS: From December 2018 to June 2021, the case data of patients with osteoporosis (T value ≤ -2.5 on dual energy X-ray bone density) who underwent posterior lumbar interbody fusion in the Fourth Medical Center, Chinese PLA General Hospital were retrospectively reviewed. All the cases were followed up for no less than 12 months and were divided into two groups according to the differences of interbody fusion materials: the autologous facet joint bone block group (autogenous bone group) and the PEEK cage group (PEEK group). The general data [such as age, gender, body mass index (BMI), primary diagnosis, distribution of fusion segments, bone mineral density of lumbar (BMD), incidence of preoperative complications], the perioperative data (such as duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate), and the incidence of postoperative complications were compared between the two groups. Imaging parameters (disc height, lumbar lordosis angle, segment lordosis angle, segmental lordosis angle, disc height improvement rate, and fusion rate) and lumbar functional scores [visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedics Association (JOA) score for lower back pain] were compared to evaluate the clinical efficacy between the kinds of intervertebral fusion materials 1 week, 3 months and 6 months postoperative and at the last follow-up. RESULTS: A total of 118 patients were enrolled, including 68 cases in the autogenous bone group and 50 cases in the PEEK group, there were no statistical differences in age, gender, BMI, primary diagnosis, distribution of fusion segments, BMD, incidence of preoperative complications, duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate, incidence of postoperative complications, all the preoperative imaging parameters and all the lumbar function scores between the two groups (P>0.05). Postoperative superficial surgical site infections occurred in 3 patients in the autogenous bone group and 2 patients in the PEEK group. At the last follow-up, 3 cases of intervertebral graft collapse occurred in the autogenous bone group and 5 cases in the PEEK group, 1 case of graft subsidence in the autogenous bone group and 1 case in the PEEK group. All the imaging parameters showed significant differences between postoperation and preoperation (P < 0.05), and all the imaging parameters showed significant differences between 1 week and 3 months postoperative in both groups (P < 0.05). The height, angle of fusion gap in the autogenous bone group were lower than those in the PEEK group 1 week postoperatively (P < 0.05), and the fusion gap height improvement rate in the autogenous bone group was lower than that in the PEEK group (P < 0.05). The cases in both groups started to show final fusion 3 months after surgery, and the fusion rate in the autogenous bone group was 75% 6 months postoperatively, which was significantly higher than the rate of 56% in the PEEK group (P < 0.05), and there was no statistically significant difference in the final fusion rate between the two groups (P>0.05). The ODI, the postoperative VAS score was significantly lower than that in preoperation, while the postoperative JOA score was significantly higher than that in preoperation (P < 0.05). The ODI was lower while the JOA score was higher of the autogenous bone group than that of the PEEK group 6 months postoperatively (P < 0.05). CONCLUSION: In osteoporosis patients, good interbody fusion rate and improvement of lumbar vertebral function can be obtained by using autologous facet joint bone block or PEEK cage, while the fusion rate and the improvement of lumbar function with autologous facet joint bone block are better than those with PEEK cage 6 months post-operatively. PEEK cage is superior to autologous facet joint bone block in intervertebral distraction and improvement of lumbar lordosis. Significant disc space subsidence occurred in osteoporotic patients within 3 months after lumbar interbody fusion, and the subsidence of PEEK cage was more obvious than that of autologous facet joint bone block.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

LncRNA XIST sponges microRNA-448 to promote malignant behaviors of colorectal cancer cells via regulating GRHL2.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential regulators in human cancers, while the role of lncRNA X-inactive-specific transcript (XIST) in colorectal cancer (CRC) via regulating miR-448 remains largely unknown. Herein, we aimed to elucidate the effect of the XIST/miR-448/grainyhead-like 2 (GRHL2) axis on CRC development. XIST, miR-448, and GRHL2 expression in CRC tissues from patients and in human CRC cell lines was assessed. Loss- and gain-function assays were implemented to unveil the roles of XIST, miR-448, and GRHL2 in screened CRC cells. The tumor growth in vivo was observed in nude mice. Binding relations among XIST, miR-448, and GRHL2 were evaluated. XIST and GRHL2 expressed highly whereas miR-448 expressed lowly in CRC tissues and cells. XIST or GRHL2 downregulation, or miR-448 elevation suppressed the malignant behaviors of CRC cells in vitro, and downregulated XIST or upregulated miR-448 also inhibited the tumor growth in vivo. miR-448 upregulation reversed the role of XIST elevation in CRC cells. XIST particularly bound to miR-448, and miR-448 targeted GRHL2. Knockdown of XIST upregulates miR-448 to impede malignant behaviors of CRC cells via inhibiting GRHL2. This study may provide novel biomarkers for CRC diagnosis and treatment.

Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.

Association of rare PPARGC1A variants with Parkinson's disease risk.

BACKGROUND: Recent researches on Parkinson's disease (PD) pathogenesis discovered the correlation between PD and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) dysfunction and reduction of PPARGC1A gene expression. Hence, we detected PPARGC1A rare variants to clarify their effect on PD risk in a large population of PD patients in mainland China. METHODS: We applied whole-exome sequencing (WES) to 1917 patients with early-onset or familial PD and 1652 controls (WES cohort), and whole-genome sequencing (WGS) to 1962 patients with sporadic late-onset PD and 1279 controls (WGS cohort). To identify PPARGC1A rare variants, we used burden analysis to assess the relationship between PPARGC1A rare variants and PD susceptibility. RESULTS: 30 rare missense variants in the cohort WES and 21 missense variants in the cohort WGS have been detected in the study and PPARGC1A missense variants are significantly associated with early-onset and familial PD susceptibility in our study (P = 0.012), which supports evidence that PPARGC1A rare variants are involved in the onset of early-onset and familial PD. CONCLUSIONS: The study suggested that PPARGC1A rare variants may contribute to the risk of early-onset and familial PD.

Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND: Abnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China. METHODS: Patients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. RESULTS: In the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=-0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission. CONCLUSIONS: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.